GRP-001 1St ESNEE Excipient Monograph: Information Needed to Formulate, Prepare and Prescribe Medicines For Neonates Containing Propylene Glycol as an Excipient
- 1Hôpital Robert Debré, Pharmacie, Paris, France
- 2ANSM, Pôle Toxicologie, Saint-Denis, France
- 3University of Liverpool, Department of Women’s and Children’s Health, Liverpool, UK
- 4University of Tartu, Neonatology, Tartu, Estonia
- 5Federal Agency for Medicines and Health Products, Afmhp, Brussels, Belgium
- 6Hôpital Antoine Béclère, Service Pharmacie, Clamart, France
Background Neonates are particularly vulnerable to the adverse effects of medicines and excipients because their organs are immature. ESNEE (European Study of Neonatal Exposure to Excipients) is a European research consortium created in 2011 after the PRIOMED-CHILD call for proposals.
Purpose The aim of ESNEE workpackage 2 was to conduct a literature review of excipients used in medicines for neonates and to establish a monograph of information for each excipient.
Materials and Methods A systematic review of the literature was conducted with 6 key databases (i.e. Medline, Web of Science, Pascal, International Pharmaceutical Abstracts, Biosis previews, Embase). Hits were selected for their relevance according to criteria set by toxicology experts. Summaries of relevant papers were prepared with underlying critical information in a table. A face to face meeting was organised with experts to validate the data. Experts from European Medicines Agency Paediatric Committee (EMA PDCO) were involved.
Results The search strategy identified around 1500 papers of which 87 were relevant to our purpose. Among those papers, 17, 20, and 15 corresponded to non-clinical, case report, and epidemiological data respectively. The remaining 35 reported miscellaneous data observed in adults. The monograph includes some general information (chemical structure, pharmaceutical use), the list of all (propylene glycol) PG-containing medicines used in Europe for neonates collected by ESNEE workpackage 1 during a point prevalence study, the kinetic characteristics of PG, the first signs of toxicity (biological perturbation, clinical signs, etc.), the organ to target for monitoring and follow up for short or long term effects, some estimations of Acceptable Daily Intake (ADI), and Permitted Daily Exposure (PDE) and finally some recommendations to manage PG toxicity.
Conclusions This is the first monograph on PG that includes the most available and relevant information validated by a panel of European experts. This documented, accurate and practical information should help the pharmaceutical industry and hospital pharmacists when formulating/preparing medicines and neonatologists when prescribing such PG-containing medicines. It also provides a clear image of which information is lacking and warrants further experimental investigation.
No conflict of interest.